Abstract

Retroviruses are known to rely extensively on the expression of viral proteins from the sense proviral genomic strand. Yet, the production of regulatory retroviral proteins from antisense-encoded viral genes is gaining research attention, due to their clinical significance. This report will discuss what is known about antisense transcription in Retroviridae, and provide new information about antisense transcriptional regulation through a comparison of Human Immunodeficiency Virus (HIV), Human T-cell Lymphotrophic Virus (HTLV-1) and endogenous retrovirus-K (ERVK) long terminal repeats (LTRs). We will attempt to demonstrate that the potential for antisense transcription is more widespread within retroviruses than has been previously appreciated, with this feature being the rule, rather than the exception.

Highlights

  • Retroviruses share a common genomic organization in which the 5′ long terminal repeat (LTR) is followed by the gag, pro, pol and env genes, and terminates with the 3′ long terminal repeats (LTRs)

  • It is noteworthy that we identified multiple Specificity Protein-1 (Sp1) binding sites in the endogenous retrovirus-K (ERVK) 3′ LTR, as they are critical for inducing transcription from TATA-less promoters

  • We have recently demonstrated the ability of IRF1 and NF-κB p65/p50 to synergistically enhance transcription from the ERVK sense promoter in the presence of select pro-inflammatory cytokines [52, 53]

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Summary

Introduction

Retroviruses share a common genomic organization in which the 5′ long terminal repeat (LTR) is followed by the gag, pro, pol and env genes, and terminates with the 3′ LTR. Retroviral antisense transcription has been largely overlooked as a source of viral RNA and proteins. There is accumulating evidence of antisense transcription in numerous exogenous retroviral genera, including lentiviruses, deltaretroviruses, gammaretroviruses and betaretroviruses. The expression of antisense proteins may be a broad phenomenon occurring across Retroviridae, suggesting that antisense encoded genes are an integral part of the viral genome. This report contributes to our understanding of antisense transcription by characterizing exogenous and endogenous retroviral 3 (antisense) promoters. Our results highlight that antisense transcription may be more widespread than previously appreciated, with endogenous retroviruses (ERVs) incapable of antisense transcription being the exception, rather than the rule

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